The major lipids of the liver, bile and gut are organized into well defined supramolecular structures such as membranes, mixed micelles, liquid crystals and emulsions. In certain disease states, the delicate physical-chemical balance of these lipids is disturbed leading to an accumulation of a particular lipid species, such as abnormal canalicular membranes in cholestasis, cholesterol monohydrate crystals in gallstones, bilirubin and bilirubinate salts in pigment stones and liquid crystals in both bile and gut luminal contents in bile salt deficiency states. Because the biliary tree and alimentary canal are predominantly aqueous systems and because of the obvious importance of the physical state of lipids and lipid interactions in aqueous systems we propose to continue the application of physical-chemical rationale and biophysical and physiological techniques to study the phase equilibria and physical state of aqueous model systems of lipids important in the function and malfunction of bile, liver cell plasma membranes and gut luminal contents and to examine the fine structure and physical characteristics of the phases found. We will then correlate the information obtained in these model systems with actual physiological and pathological phenomena, namely 1) bile and cholesterol gallstones, 2) bilirubin and pigment stones, 3) the structure and function of canalicular membranes and 4) the digestion and absorption of fat. Our attempts to understand the pathophysiology of lipid related diseases of the alimentary tract at a molecular level will consist of a multi-disciplinary approach both in terms of the chemical, biochemical, physical and physiological methodology we will employ and the education, background, training and expertise of our research personnel.